LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA-1 IN DEVELOPING MUSCLES - IMPLICATIONS FOR CONNECTIVE-TISSUE AND FIBER-TYPE PATTERN-FORMATION

Skeletal muscles are highly ordered mixtures of cell types, with each muscle having its own characteristic pattern of fiber types, connectiv e tissues, and vasculature. The precursors of the myogenic and connect ive elements of a muscle are initially intermixed and are proliferatin g and differentiating together in a manner that generates an ordered a rray of mature cells. The molecular basis of myogenesis is unknown, al though in vitro studies have revealed numerous putative regulators. Th e results obtained from in vitro studies are not easily related to in vivo myogenesis because of a lack of information about the localisatio n of the putative regulators in developing muscles. The objective of t his paper was therefore to describe the spatial and temporal distribut ion of transforming growth factor beta 1 (TGF-beta 1), a small peptide that affects cultured fibroblasts, myoblasts, and vascular endothelia l cells. TGF-beta 1-immunoreactivity was associated with the epimysia, perimysia, and vasculature of the developing muscles. The expression of TGF-beta 1 within developing muscles had a distinct spatial and tem poral pattern that correlated with the fate of adjacent myotubes. Myot ubes which formed prior to the expression of TGF-beta 1 developed into slow fibers whereas those which formed adjacent to TGF-beta 1-contain ing connective tissue matured into fast fibers. The possibility that T GF-beta 1 is involved in the generation of the pattern of epi- and per imysia and/or fiber types is discussed.